Colon cancer specialists questioned SillaJen’s allegation that the combination of SillaJen’s Pexa-Vec and AstraZeneca’s Imfinzi worked well in colorectal cancer patients who did not respond to immune checkpoint inhibitors.
SillaJen said on Wednesday that in a trial sponsored by the U.S. National Cancer Institute (NCI) on the combo therapy of Pexa-Vec and Imfinzi, one patient with microsatellite instable-low (MSI-L) cancer whose tumor spread to the liver and the lungs showed a partial response (PR) of a reduced tumor.
“The patient’s carcinoembryonic antigen (CEA), a tumor marker, returned to normal and the use of analgesics to control pain decreased as well,” the company said in a news release.
Colorectal cancer generally appears in two types – MSI-H (microsatellite instable-low) and MSI-L. MSI-H type accounts for 15 percent, and MSI-L, 85 percent. While patients with MSI-H colon cancer can use FDA-authorized immune checkpoint inhibitors, MSI-L patients do not respond to them at all with any other treatment option, SillaJen said.
“We can say that using Pexa-Vec with an immune checkpoint inhibitor enhanced anti-tumor immunity. It is meaningful that an MSI-L patient, whose response to any immune checkpoint inhibitor was zero, had a partial response,” the company said.
The U.S. trial is still in progress on 35 patients who did respond to curative resection or who have microsatellite-stable (MSS) colorectal cancer. The patients are divided into two groups – Pexa-Vec+Imfinzi group and Pexa-Vec+Imfinze+tremelimumab group. The patient who had a partial response was in the former group.
However, local physicians said SillaJen’s press release was an exaggeration.
The company’s premise -- that MSI-L colorectal patients had no treatment option because they do not respond to immune checkpoint inhibitors -- was wrong, they said. Under a false assumption, it was not reasonable to interpret a single patient’s partial response as a success to confirm the drug’s efficacy, they said.
“It is wrong to say that patients who are not MSI-H do not respond to any immune checkpoint inhibitor. A study reported that immune checkpoint inhibitors could work in those who have POLE genetic mutation or other genetic mutation relating to DAN damage recovery,” said a professor at the oncology department at a university hospital.
“The effectiveness might have stemmed from an unknown mechanism. It is too much to say that the combo reinforced immunity with a single patient case. Publishing a press release on a patient’s case in the middle of a trial could create a problem in the future,” he added.
Another oncology professor at another university hospital also expressed a similar opinion. “It is difficult to say the Pexa-Vec+Imfinzi treatment induced a partial response in one patient,” he said.
Physicians expressed concern that a premature interpretation of a trial in progress could mislead investors.
In response to the concern, SillaJen said the news release was merely the delivery of the fact that the combo therapy showed such efficacy, not more or not less.
“Tim F. Greten, M.D. at NCI, who is the principal investigator of the trial, shared his opinion that it was meaningful to see such efficacy while MSI-L colon cancer does not respond to an immune checkpoint inhibitor. It was the investigator’s opinion, not a conclusion of the trial,” an official at SillaJen said.
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